bromodomain inhibitor 8

Bromodomain inhibitor-8 is an inhibitor of BET bromodomain used to treat autoimmune and inflammatory diseases.

PBRM1-BD2-IN-8 (compound 34) 是一种强效的 PBRM1 Bromodomain 抑制剂 (PBRM1-BD2 Kd=4.4 μM, PBRM1-BD2 IC50=0.16 μM; PBRM1-BD5 Kd=25 μM)，其具有抗癌活性。

I-BET282E 是八种 BET bromodomains 泛抑制剂，对其他代表性含溴代烷的蛋白质表现出选择性。I-BET282E 能够作用于 8 种 BRD2 (BD1 BD2), BRD2 (BD1 BD), BRD3 (BD1 BD), BRD4 (BD1 BD) ，他们的 pIC50值为 6.4-7.7。

CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC50= 0.71 μM), as well as class I histone deacetylases (HDACs; IC50s = 0.046, 0.058, 0.075, and 0.167 μM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC50s = 0.073 and 0.923 μM for HDAC6 and HDAC10, respectively).1It is selective for these enzymes over BRD2, -3, and -T (IC50s = >20 μM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC50s = >10 μM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC50s = 0.45, 1.78, and 2.11 μM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg. 1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)

BAY-299是一种有效的抑制剂，能抑制 bromodomain 和 PHD 指家族成员 BRPF2以及 TATA 盒结合蛋白相关因子 TAF1和 TAF1L，其IC50分别为67 nM、8 nM 和106 nM。

HDAC6 8 BRPF1-IN-1 is a dual inhibitor that targets HDAC6, HDAC8, and the bromodomain and PHD finger containing protein 1 (BRPF1). It exhibits inhibitory activity against HDAC1, HDAC6, and HDAC8 with IC50 values of 797 nM, 344 nM, and 908 nM, respectively. In addition, it inhibits BRPF1 with a Kd value of 175.2 nM. This compound is utilized in cancer research [1].

IACS-9571 (trifluoroacetate),作为溴结构域蛋白TRIM24和BRPF1的抑制剂,展示了对TRIM24的强效抑制活性,其IC50和Kd值分别达到8 nM和31 nM,而对BRPF1的Kd值则为14 nM.

EN219 is a synthetic recruiter of the E3 ubiquitin ligase RNF114.1It binds to cysteine 8 (C8) in the intrinsically disordered region of RNF114 (RNF114-C8; IC50= 470 nM) and inhibits RNF114-induced autoubiquitination and p21 ubiquitination in a cell-free assay when used at a concentration of 50 μM. EN219 (1 μM) also interacts with cysteine residues in the tubulin β1 chain (TUBB1), heat shock protein 60 (Hsp60), also known as Hsp family D member 1 (HspD1), and histone H3.1 (HIST1H3A) in 231MFP human breast cancer cells in a proteomic profiling assay. It has been linked to the bromodomain and extra terminal domain (BET) inhibitor ligand (+)-JQ1 for use as a proteolysis-targeting chimera (PROTAC) to degrade bromodomain-containing protein 4 (BRD4) in 231MFP cells. 1.Luo, M., Spradlin, J.N., Boike, L., et al.Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product functionCell Chem. Biol.28(4)559-566(2021)